NM_175723.2:c.239A>T

Variant names:

• chrX-48194170-T-A
• rs782033607
• NM_175723.2:c.239A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175723.2(SSX5):​c.239A>T​(p.Gln80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q80H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 21)
• Consequence: SSX5 NM_175723.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 0 publications found

Genes affected

SSX5 (HGNC:11339): (SSX family member 5) The product of this gene belongs to the family of highly homologous synovial sarcoma X (SSX) breakpoint proteins. These proteins may function as transcriptional repressors. They are also capable of eliciting spontaneous humoral and cellular immune responses in cancer patients, and are potentially useful targets in cancer vaccine-based immunotherapy. While some of the related SSX genes are involved in t(X;18)(p11.2;q11.2) translocations that are characteristically found in all synovial sarcomas, this gene does not appear to be involved in such translocations. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16058078).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175723.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX5	NM_175723.2	MANE Select	c.239A>T	p.Gln80Leu	missense	Exon 4 of 8	NP_783729.1	O60225-1
	SSX5	NM_021015.4		c.362A>T	p.Gln121Leu	missense	Exon 5 of 9	NP_066295.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX5	ENST00000347757.6	TSL:5 MANE Select	c.239A>T	p.Gln80Leu	missense	Exon 4 of 8	ENSP00000290558.1	O60225-1
	SSX5	ENST00000311798.5	TSL:5	c.362A>T	p.Gln121Leu	missense	Exon 5 of 9	ENSP00000312415.1	O60225-2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.96
DEOGEN2	Benign	0.073	T
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-2.1
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.087
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.011	D
Polyphen		0.77	P
Vest4		0.23
MutPred		0.28		Loss of disorder (P = 0.0297)
MVP		0.067
MPC		0.033
ClinPred		0.78	D
GERP RS		-3.4
Varity_R		0.097
gMVP		0.046
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs782033607; hg19: chrX-48053606;